Artículo
Saliva as a noninvasive biological sample to compare bioavailability of phenytoin formulations by LC-MS/MS
Baldo, Matias Nicolas
; Hunzicker, Gabriel Alejandro
; Altamirano, Jorgelina Cecilia
; Murguia, Marcelo Cesar
; Hein, Gustavo Juan
Fecha de publicación:
09/2015
Editorial:
Elsevier
Revista:
International Journal of Pharmaceutical Sciences and Research
ISSN:
2320-5148
e-ISSN:
0975-8232
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
The use of noninvasive biological samples such as saliva, it is of great interest for therapeutic drug monitoring (TDM), including the anticonvulsants Phenytoin (PHT). A simple analytical methodology by liquid chromatography-tandem mass spectrometry was developed and validated to carry out a relative comparative bioavailability (RBA) study of two PHT formulations in human plasma and saliva and the subsequent correlation between both matrixes. A single-dose, randomized-sequence, open-label, two-way crossover study, was conducted in 24 healthy Latin American male volunteers. The bioequivalence of 200 mg PHT tablet was evaluated using plasma and saliva to determine Cmax, Tmax, AUC0-t and AUC0-∞. Figures of merit of the proposed methodology were as follows: linear ranges of 40-5055 ng/mL and 5-1340 ng/mL for plasma and saliva, respectively, with a correlation coefficient of (r)>0.999. The LOD and LOQ were 15 ng/mL -40ng/mL for plasma and 1.5 ng/mL – 5.0 ng/mL for saliva. Accuracy, precision (as %CV) and recovery were accepted according the bioequivalence criteria. Stability showed %bias<15%. The PHT saliva/PHT plasma ratios for all parameters were: 5.4, 2.2, 1.4 for Cmax, and 1.7, 1.2, 1.1 for AUC. Plasma and saliva results were correlated (R=0.9889 and R=0.9947 for Reference and Test, respectively). Saliva not only is a suitable matrix for RBA studies and TDM, but also a more convenient tool since it provides analogous information with mayor analytical, ethical, and biosafety advantages. However, an additional pre-study of product dissolution in oral cavity is suggested before carrying out complete RBA studies for prompt-release drugs
Palabras clave:
Phenytoin
,
Saliva
,
Bioequivalence
,
Lc-Ms/Ms
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(IANIGLA)
Articulos de INST. ARG. DE NIVOLOGIA, GLACIOLOGIA Y CS. AMBIENT
Articulos de INST. ARG. DE NIVOLOGIA, GLACIOLOGIA Y CS. AMBIENT
Articulos(ICIVET-LITORAL)
Articulos de INST. DE CIENCIAS VETERINARIAS DEL LITORAL
Articulos de INST. DE CIENCIAS VETERINARIAS DEL LITORAL
Citación
Baldo, Matias Nicolas; Hunzicker, Gabriel Alejandro; Altamirano, Jorgelina Cecilia; Murguia, Marcelo Cesar; Hein, Gustavo Juan; Saliva as a noninvasive biological sample to compare bioavailability of phenytoin formulations by LC-MS/MS; Elsevier; International Journal of Pharmaceutical Sciences and Research; 6; 9; 9-2015; 3752-3760
Compartir
Altmétricas